Thesis (Ph. D.)--Cornell University, 1976. / Vita. Includes bibliographical references (p. 290-310).

Many of the patterns of genetic variation we observe today have arisen via the complex dynamics of interactions and isolation of historic human populations. In this thesis, we focus on two important features of the genetics of populations that can be used to learn about human history: population structure and admixture. The Iberian peninsula has a complex demographic history, as well as rich linguistic and cultural diversity. However, previous studies using small genomic regions (such as Y-chromosome and mtDNA) as well as genome-wide data have so far detected limited genetic structure in Iberia. Larger datasets and powerful new statistical methods that exploit information in the correlation structure of nearby genetic markers have made it possible to detect and characterise genetic differentiation at fine geographic scales. We performed the largest and most comprehensive study of Spanish population structure to date by analysing genotyping array data for ~1,400 Spanish individuals genotyped at ~700,000 polymorphic loci. We show that at broad scales, the major axis of genetic differentiation in Spain runs from west to east, while there is remarkable genetic similarity in the north-south direction. Our analysis also reveals striking patterns of geographically-localised and subtle population structure within Spain at scales down to tens of kilometres. We developed and applied new approaches to show how this structure has arisen from a complex and regionally-varying mix of genetic isolation and recent gene-flow within and from outside of Iberia. To further explore the genetic impact of historical migrations and invasions of Iberia, we assembled a data set of 2,920 individuals (~300,000 markers) from Iberia and the surrounding regions of north Africa, Europe, and sub-Saharan Africa. Our admixture analysis implies that north African-like DNA in Iberia was mainly introduced in the earlier half (860 - 1120 CE) of the period of Muslim rule in Iberia, and we estimate that the closest modern-day equivalents to the initial migrants are located in Western Sahara. We also find that north African-like DNA in Iberia shows striking regional variation, with near-zero contributions in the Basque regions, low amounts (~3%) in the north east of Iberia, and as high as (~11%) in Galicia and Portugal. The UK Biobank project is a large prospective cohort study of ~500,000 individuals from across the United Kingdom, aged between 40-69 at recruitment. A rich variety of phenotypic and health-related information is available on each participant, making the resource unprecedented in its size and scope. Understanding the role that genetics plays in phenotypic variation, and its potential interactions with other factors, provides a critical route to a better understanding of human biology and population health. As such, a key component of the UK Biobank resource has been the collection of genome-wide genetic data (~805,000 markers) on every participant using purpose-designed genotyping arrays. These data are the focus of the second part of this thesis. In particular, we designed and implemented a quality control (QC) pipeline on behalf of the current and future use of this multi-purpose resource. Genotype data on this scale offers novel opportunities for assessing quality issues, although the wide range of ancestral backgrounds in the cohort also creates particular challenges. We also conducted a set of analyses that reveal properties of the genetic data, including population structure and familial relatedness, that can be important for downstream analyses. We find that cryptic relatedness is common among UK Biobank participants (~30% have at least one first cousin relative or closer), and a full range of human population structure is present in this cohort: from world-wide ancestral diversity to subtle population structure at sub-national geographic scales. Finally, we performed a genome-wide association scan on a well-studied and highly polygenic phenotype: standing height. This provided a further test of the effectiveness of our QC, as well as highlighting the potential of the resource to uncover novel regions of association.

Abstract Natural selection, mutation, recombination, demographic history and chance all have a role in evolution. In natural populations, the outcome of these forces is seen as adaptations, differences between geographic varieties, and as genetic diversity in populations—both at the phenotypic and molecular levels. In this thesis I wanted to examine the roles of the evolutionary forces shaping molecular genetic diversity in trees, with emphasis on a boreal conifer, Scots pine (Pinus sylvestris). Phylogeographic history and past population size changes have a dominant role in molecular diversity of P. sylvestris. The effect of the Last Glacial Maximum (37 000–16 000) was observed in the distribution of mitochondrial DNA variation. In contrast, nuclear DNA was not much affected by the last glacial period. Instead, more ancient demographic events that took place millions of years ago can still be observed in the variation of P. sylvestris nuclear DNA. Not much evidence of positive natural selection was found in pines or trees in general. This is in contrast to strong natural selection that is observed at the phenotypic level. Positive selection is difficult to prove, especially when the genome is still affected by demographic history. Mutation–drift equilibrium may rarely be reached in tree populations.

As tartarugas marinhas são répteis de vida longa que realizam extensas migrações entre áreas de alimentação e desova, resultando em estágios sucessivos de mistura e isolamento de estoques genéticos, espacial e temporalmente. A tartaruga-verde (Chelonia mydas) está ameaçada de extinção, e é fundamental entender sua dinâmica populacional e distribuição para o manejo e conservação da espécie. O objetivo deste estudo foi analisar a diversidade genética, estrutura populacional, origens dos indivíduos e história demográfica de C. mydas em três locais do Oceano Atlântico (estado do Rio de Janeiro, Brasil - área de alimentação; Guadalupe e Guiana Francesa - áreas de desova), com base em sequências da região controle do DNA mitocondrial (mtDNA) e 10 loci de microssatélites. As análises de mtDNA demonstraram que a área amostrada no Brasil tem perfil genético semelhante às outras áreas de alimentação da costa brasileira. De maneira semelhante, o perfil genético das duas áreas de desova é bastante similar ao de outros sítios reprodutivos na região do Caribe. As análises de estoque misto revelaram que os indivíduos juvenis no Brasil são provenientes principalmente da Ilha Ascensão, Guiana Francesa e Guiné Bissau. Os microssatélites detectaram estrutura genética entre as três populações, apesar de haver um fluxo de migrantes entre elas, especialmente de indivíduos da Guiana Francesa em direção ao Brasil e Guadalupe. Guiana Francesa, Guadalupe e Brasil apresentaram declínio populacional severo, detectado pelos microssatélites. Apesar da distribuição global, as populações de tartarugas-verdes estão sujeitas a diferentes pressões nos habitats que ocupam, e é importante entender quais populações estão ameaçadas. Este estudo enfatiza a importância da conectividade entre áreas de alimentação e desova que podem estar amplamente distribuídas de acordo com oportunidades ou restrições ecológicas, adicionando informações a respeito da dispersão e a dinâmica de tartarugas-verdes que frequentam o Oceano Atlântico / Sea turtles are reptiles with a long lifespan that undertake wide-ranging migrations through feeding and nesting sites, resulting in successive stages of mixing and isolating genetic stocks, both spatially and temporally. The green sea turtle (Chelonia mydas) is threatened with extinction, and it is essential to understand its population dynamics and distribution in order to manage and preserve the species. The aim of this study was to analyze the genetic diversity, population structure, natal origins and demographic history of C. mydas in three sites in the Atlantic Ocean (Rio de Janeiro state, Brazil - feeding ground; Guadeloupe and French Guiana - nesting sites), based on sequences of the mitochondrial DNA (mtDNA) control region and 10 microsatellites loci. The mtDNA analyses demonstrated that Brazilian samples have the same genetic profile of others collected in feeding grounds in the Brazilian coast. Similarly, the genetic profile of the nesting sites has resemblances to others in the Caribbean region. The mixed stock analyses revealed that most of the juveniles in Rio de Janeiro state come from Ascension Island, French Guiana and Guinea Bissau. Microsatellites detected genetic structure among the three populations, even with migration flows, especially in individuals from French Guiana to Brazil and Guadeloupe. French Guiana, Guadeloupe and Brazil presented a severe population decline, detected by the microsatellites analyses. Despite the worldwide distribution, green sea turtle populations undergo different pressures at the habitats they occupy, and it is important to understand which populations are threatened. This study emphasizes the importance of connecting nesting and feeding areas that can be widely distributed according to ecological opportunities or constraints, adding information on dispersion and population dynamics of green sea turtles on Atlantic Ocean

京都大学 / 新制・課程博士 / 博士(理学) / 甲第24310号 / 理博第4880号 / 新制||理||1698(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 曽田 貞滋, 准教授 渡辺 勝敏, 教授 中務 真人 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

Yes / Plant mating systems have profound effects on levels and structuring of genetic variation and can affect the impact of natural selection. Although theory predicts that intermediate outcrossing rates may allow plants to prevent accumulation of deleterious alleles, few studies have empirically tested this prediction using genomic data. Here, we study the effect of mating system on purifying selection by conducting population-genomic analyses on whole-genome resequencing data from 38 European individuals of the arctic-alpine crucifer Arabis alpina. We find that outcrossing and mixed-mating populations maintain genetic diversity at similar levels, whereas highly self-fertilizing Scandinavian A. alpina show a strong reduction in genetic diversity, most likely as a result of a postglacial colonization bottleneck. We further find evidence for accumulation of genetic load in highly self-fertilizing populations, whereas the genome-wide impact of purifying selection does not differ greatly between mixed-mating and outcrossing populations. Our results demonstrate that intermediate levels of outcrossing may allow efficient selection against harmful alleles, whereas demographic effects can be important for relaxed purifying selection in highly selfing populations. Thus, mating system and demography shape the impact of purifying selection on genomic variation in A. alpina. These results are important for an improved understanding of the evolutionary consequences of mating system variation and the maintenance of mixed-mating strategies. / This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1707492115/-/DCSupplemental.

The clouded apollo (Parnassius mnemosyne) is a palearctic butterfly with a wide distribution across Eurasia. In recent decades, however, the species has declined in many parts of its distribution range. In Sweden, both the distribution and populations size of the clouded apollo has decreased dramatically over the past two decades, mainly due to habitat loss resulting from changes in land use practices. Today, only three geographically isolated populations remain in Sweden, as well as one captive population. While previous studies have explored the population genetics of other clouded apollo populations across Eurasia, little is known about the genetics of the remaining populations in Sweden. Here we make use of whole genome resequencing data from clouded apollo individuals collected in each of the three natural populations as well as the captive population. We apply population genetic analyses and explore mitochondrial gene data when mapping to two different reference genome assemblies, to get a better understanding of the genetic structure and levels of genetic diversity of the populations in Sweden. Our results show that the clouded apollo populations in different geographic regions harbour similar but relatively low levels of genetic diversity. We also find significant genetic differentiation between the northernmost population and the populations in southern Sweden, as well as higher levels of inbreeding in this population. Our analysis of the mitochondrial CO1 gene coupled with previously available data, shows that the remaining clouded apollo populations in Sweden correspond to two distinct mitochondrial haplogroups characteristic of different regions of Eurasia. Together with our other results, this indicates a re-colonisation of Scandinavia via two different routes after the last glacial maximum. Finally, our analyses uncover sub-population substructure in one of the remaining populations in southern Sweden. Together our results provide a first overview of the populations genetics of the clouded apollo butterfly in Sweden and explore the genetic consequences of populations size declines and fragmentation in the region. These findings were communicated to local conservation authorities and used to inform conservation strategies to protect this endangered species in Sweden.

A associação não aleatória entre alelos de diferentes lócus caracteriza o que é chamado de desequilíbrio de ligação (DL) entre eles. A extensão do DL nas populações humanas pode ser influenciada por muitos fatores, tais como taxa de recombinação, características demográficas (idade, tamanho e taxa de crescimento) e fatores evolutivos (deriva genética, efeito fundador, gargalos populacionais, mutação, seleção e fluxo gênico). Portanto, o conhecimento dos padrões do DL fornecem dados que auxiliam na descrição dos eventos demográficos e evolutivos sofridos pelas populações. O objetivo deste estudo foi descrever os padrões de DL de quatro populações brasileiras e correlacioná-los com suas respectivas histórias demográficas, uma vez que estas populações experimentaram alguns dos eventos evolutivos que geram ou retardam o decréscimo do DL, como fundação por poucos indivíduos, miscigenação no momento da fundação e posterior isolamento. Foram analisadas amostras de três populações remanescentes de quilombos do Estado do Piauí, Gaucinha (GAU, n = 14), Mimbó (MIB, n = 15) e Sítio Velho (STV, n = 15) e da população urbana de Teresina, Piauí (TES, n = 15), além de sete amostras populacionais do projeto HapMap (CEU, CHB, JPT, ASW, LWK, MKK, YRI, todas com n = 15). Foram genotipados mais de 250 mil SNPs (Single Nucleotide Polymorphisms) utilizando-se o GeneChip® Human Mapping 250K Nsp I Array - Affymetrix® nas amostras das quatro populações brasileiras. Os dados brutos das populações do HapMap para este array foram obtidos na página do projeto. Os genótipos para todas as amostras foram determinados pelo algoritmo CRLMM após comparação com o algoritmo BRLMM, e as análises de DL e determinação dos blocos de haplótipos foram realizadas com o uso do programa Haploview. Considerando-se o número de blocos de haplótipos detectados em cada população estudada, padrão semelhante foi observado em todos os autossomos. Em geral, a população europeia (CEU) e as duas populações asiáticas (CHB e JPT) do HapMap apresentaram os maiores números de blocos, enquanto que os menores números foram observados nos quilombos GAU e MIB e na população TES. As populações africanas LWK, MKK e YRI e a população afro-americana ASW apresentaram os valores intermediários e a população afro-brasileira STV, apresentou um número de blocos apenas inferior a CEU, CHB e JPT. A grande contribuição africana nos quilombos GAU e MIB pode explicar o menor DL observado nestas comunidades. Por outro lado, o menor DL em TES se deve, provavelmente, à sua fundação, que envolveu um maior número de indivíduos e foi seguida por um rápido crescimento. A possível explicação para o maior DL observado em STV, em relação aos demais quilombos, consiste em sua peculiar história demográfica: esta comunidade experimentou uma miscigenação no momento de sua fundação, que foi seguida por um crescimento lento e pouca diferenciação. Assim, foi demonstrado como os eventos demográficos de cada população influenciam seus respectivos padrões de DL. / The non-random association between alleles of different loci characterizes what is called linkage disequilibrium (LD) between them. The LD extent in human populations can be influenced by many factors, such as recombination rate, demographic features (age, size and growth rate) and evolutionary events (genetic drift, founder effects, population bottlenecks, mutation, selection and gene flow). Therefore, knowledge of the LD patterns provides data that assists in describing the evolutionary and demographic events experienced by populations. The aim of this study was to describe the LD patterns of four Brazilian populations and correlate these patterns with their respective demographic histories, since these populations have experienced some of the evolutionary events that produce or retard the LD decrease, such as foundation by few individuals, admixture at the founding moment and subsequent isolation. Samples from three quilombo remnants populations of the Piauí State, Gaucinha (GAU, n = 14), Mimbó (MIB, n = 15) and Sítio Velho (STV, n = 15) and the urban population of Teresina, Piauí (TES, n = 15), and seven population samples from the HapMap Project (CEU, CHB, JPT, ASW, LWK, MKK, YRI, all with n = 15) were analyzed. More than 250 thousand SNPs (Single Nucleotide Polymorphisms) were genotyped using the GeneChip ® Human Mapping 250K Nsp Array I - Affymetrix ® in the samples of the four Brazilian populations. Raw data of the HapMap population samples for this array were obtained from the HapMap homepage. Genotypes for all samples were determined by CRLMM algorithm after comparison with the BRLMM algorithm. LD analyzes and determination of haplotype blocks were performed using the Haploview software. Considering the number of haplotype blocks detected in each population, a consistent pattern was observed for all autosomes. The European population (CEU) and the two Asian populations (CHB and JPT) of the HapMap showed the highest numbers of blocks, while the lowest numbers were observed in the GAU and MIB quilombos and in the TES population. The African populations, LWK, MKK and YRI, and the African-American ASW exhibited intermediate values and the African-Brazilian population STV, presented a number of blocks smaller than that observed for CEU, CHB and JPT. The great African contribution in the GAU and MIB quilombos may explain the lower LD observed in these communities. On the other hand, the lower LD in TES is probably due to its foundation that involved a larger number of individuals and was followed by a fast growth. A possible explanation for the higher LD observed in STV, compared to other quilombos, consists in its particular demographic history: this community experienced admixture at the time of its foundation, which was followed by slow growth and low differentiation. Thus, it was shown how the demographic events of each population influence their respective LD patterns.

We investigated the population dynamics of the giant water bug, Belostoma angustum, across highland sin the Pampas of southern Brazil. We evaluated genetic and morphological variation, as well as the demographic history of 18 populations. The overall range includes two highlands and a lowland between them, overall exceeding 400 kilometers along the longitudinal gradient. Genetic variation was assessed from mitochondrial and nuclear markers. The morphological variation was estimated using linear measurements of males and females, and from male genitalic structures using geometric morphometrics approaches. We evaluated the effect of the highland topography, drainage basins, and past climate changes on the population structure. Our results from multiple analyses of molecular variance (AMOVA) show that Belostoma angustum structures as a large panmictic population across the Pampas highlands range. Every most frequent haplotype is shared by individuals from all three sampled areas in genetic markers from the mitochondrial as well as from the nuclear locus. Differentiation among haplotypes was very low, not greater than two mutation steps. The congruent phylogeographical pattern in both markers indicate absent sex-biased migration rates. Furthermore, there was no evidence for isolation-by-distance (IBD) based on the mitochondrial data. The pairwise st was low and not significant, indicating historical gene flow among populations of the giant water bug studied throughout Pampas highlands. Our findings about the demographic history of panmictic population throughout Pampas highlands suggest it experienced recent and rapid population expansion that started in the Late Pleistocene period, approximately 15,000 years old after Last Glacial Maximum. The recent marked demographic expansion could explain the high percentage of the exclusive haplotypes and the very low mutational steps among them. We did not find morphological variation among populations of B. angustum throughout Pampas highlands reflected, except for some body dimensions. The overall phenotypic uniformity among populations becomes more likely if gene flow is hypothesized to homogenize populations. However, in the body size, specially, there was variation among populations potentially explained by phenotypic plasticity, thereby generating phenotypic diversity without genetic differentiation. Our genetic findings suggest indirectly that individuals of B. angustum are strong fliers able to overcome the topographical barriers of the sampled area. / Neste trabalho, investigamos a dinâmica populacional de uma barata d\' água, Belostoma angustum, ao longo do Pampa no sul do Brasil. Foram avaliadas a variação genética, morfológica e a história demográfica de 18 populações. A área total amostrada inclui duas serranias e uma planície entre elas, excedendo 400 quilômetros ao longo de um gradiente longitudinal. A variação genética foi avaliada a partir de marcadores mitocondriais e nucleares. A variação morfológica foi avaliada utilizando medidas lineares de machos e fêmeas, e de estruturas genitais masculinas usando abordagens de morfometria geométrica. Testamos o efeito da topografia das serranias, das bacias de drenagem e das mudanças climáticas passadas sobre a estrutura das populações. Os resultados de múltiplas análises de variância molecular (AMOVA) mostram que Belostoma angustum forma uma grande população panmítica ao longo das serranias do Pampa. Todos os haplótipos mais frequentes são compartilhados por indivíduos de todas as três grandes áreas amostradas em marcadores genéticos dos loci mitocondrial e nuclear. A diferenciação entre haplótipos foi muito baixa, não excedendo dois passos mutacionais. O padrão filogeográfico congruente em ambos os marcadores indica taxas de migração não enviesada para um dos sexos. Além disso, não encontramos evidência de isolamento por distância (IBD) com base nos dados mitocondriais. Os valores de st par a par foram baixos e não significativos, indicando fluxo gênico histórico entre as populações da barata d\'água estudada ao longo das serranias Pampianas. Os resultados sobre a história demográfica da população panmítica ao longo do planalto do Pampa sugerem que essa população experimentou uma expansão populacional recente e rápida que teve início no fim do período Pleistoceno (há aproximadamente 15.000 anos), após a última máxima glacial. A expansão demográfica recente e acentuada poderia explicar a alta porcentagem de haplótipos exclusivos e o número reduzido de passos mutacionais entre eles. Não encontramos variação morfológica entre as populações de B. angustum amostradas ao longo das serranias do Pampa, exceto em algumas dimensões corporais. A uniformidade fenotípica entre as populações torna-se mais provável na medida em que o fluxo de genes atue homogeneizando as populações. Entretanto, no caso do tamanho do corpo, especialmente, há variação entre populações potencialmente explicada por plasticidade fenotípica, gerando assim diferenciação fenotípica sem diferenciação genética. Nossos resultados genéticos sugerem indiretamente que os indivíduos de B. angustum possuem capacidade de voo suficiente para transpor as barreiras topográficas na área amostrada.

Made available in DSpace on 2017-07-21T14:49:48Z (GMT). No. of bitstreams: 1 Leticia Leal de Almeida.pdf: 1169651 bytes, checksum: c5d2f194225826a19029ebcacaa885bc (MD5) Previous issue date: 2017-02-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The present work analyzes the historiographical production of Altiva Pilatti Balhana (1929-2009) understood from 1950, when the first interests of research arise, influenced by Geography and Anthropology, in the Faculty of Philosophy, Sciences and Letters and how Balhana delimited his interests in the history of immigration, integrating the faculty of the said Faculty in 1958, defending in 1959 his thesis of Free Teaching: Santa Felicidade: a process of assimilation. Balhana, together with Cecília Maria Westphalen (1927-2004), participated in the institutionalization of the Department of History of the University of Paraná in 1959, defined the bases and guidelines of the newly separated History of Geography and established an academic historiography at the University of Paraná. In the Department of History, Balhana and the other teachers organize a conception of History and the office of the historian who guided research projects, organization of sources and archives, especially from the reference of the Annales problem history. Balhana appropriated concepts and categories to apprehend the past, stemming from his interests in Immigration History, appropriated also the French Demographic History, developed by Louis Henry and Michel Fleury. Of the developments in the organization of historiography at the University of Paraná, a Postgraduate Program was created at Masters level in 1972, with a research line in Economic and Demographic History. Balhana and the other professors contributed to the consolidation and recognition of the historiography of the History Department of the University of Paraná, together with the Brazilian historiography. / O presente trabalho analisa a produção historiográfica de Altiva Pilatti Balhana (1929-2009) compreendida a partir de 1950, momento em que surgem os primeiros interesses pela pesquisa, influenciada pela Geografia e Antropologia, na Faculdade de Filosofia, Ciências e Letras e como Balhana delimitou seus interesses em torno da história da imigração, integrando o corpo docente da referida Faculdade em 1958, defendendo em 1959 sua tese de Livre-Docência: Santa Felicidade: um processo de assimilação. Balhana, junto à Cecília Maria Westphalen (1927-2004), participou da institucionalização do Departamento de História da Universidade do Paraná em 1959, definiu as bases e diretrizes da História recém-separada da Geografia e instaurou uma historiografia acadêmica na Universidade do Paraná. No Departamento de História, Balhana e os demais professores organizam uma concepção de História e do ofício do historiador que norteou projetos de pesquisas, organização de fontes e arquivos, sobretudo a partir da referência da história-problema dos Annales. Balhana apropriou-se de conceitos e categorias para apreensão do passado, decorrentes dos seus interesses em História da imigração, apropria-se também da História Demográfica francesa, desenvolvida por Louis Henry e Michel Fleury. Dos desdobramentos da organização da historiografia na Universidade do Paraná, fora criado Programa de Pós-Graduação, em nível de Mestrado, em 1972, com uma linha de pesquisa em História Econômica e Demográfica. Balhana e os demais professores, contribuíram para a consolidação e reconhecimento da historiografia do Departamento de História da Universidade do Paraná junto à historiografia brasileira.